Synthesis, Spectroscopic, and in Vitro Photosensitizing Efficacy of Ketobacteriochlorins Derived from Ring-B and Ring-D Reduced Chlorins via Pinacol–Pinacolone Rearrangement

Abstract

In this report we present a regioselective oxidation of a series bacteriochlorins, which on reacting with either ferric chloride (FeCl3) or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) yielded the corresponding ring-B or ring-D reduced chlorins. The effect of the number of electron withdrawing groups present at the peripheral position, with or without a fused isocyclic ring (ring-E) did not make any significant difference in regioselective oxidation of the pyrrole rings. However, depending on the nature of substituents, the intermediate bis-dihydroxy bacteriochlorins on subjecting to Pinacol-Pinacolone reaction conditions gave various ketochlorins. The introduction of the keto- group at a particular position in the molecule possibly depends on the stability of the intermediate carbocation species. The newly synthesized bacteriochlorins show strong long-wavelength absorption and produced significant in vitro (Colon26 cells) photosensitizing ability. Among the compounds tested, the bacteriochlorins containing a keto-group at position-7 of ring-B with cleaved 5-member isocyclic ring showed the best efficacy.

Asymmetric Synthesis of a Bacteriochlorophyll Model Compound Containing trans-Dialkyl Substituents in Ring D

“…Relatively few ring-B chlorins containing an intact isocyclic ring are known (Scheme 8, bottom), all of which have been prepared by semisynthesis beginning with bacteriochlorophyll a (by selective dehydrogenation with FeCl 3 ) 59,60 or a porphyrin derived from chlorophyll a (by selective vicinal hydroxylation with OsO 4 ). 61 The known ring-B chlorins exhibit the following red-region absorption properties: C-2, λ = 691 nm, ε 691nm = 4.31 × 10 4 M −1 cm −1 (CH 2 Cl 2 ); 59 C-3, λ = 682 nm, ε 682nm = 3.65 × 10 4 M −1 cm −1 (CH 2 Cl 2 /THF); 60 and C-4, λ = 683 nm (CH 2 Cl 2 ). 61 The availability of C-1 provided a valuable marker to address one of the key questions posed at the outset of this research, namely, does adventitious dehydrogenation occur during the course of macrocycle formation leading to a chlorin byproduct accompanying the bacteriochlorin BC-1?…”

“…Treatment of hydroporphyrins with the high-potential quinone DDQ is well established, and with native bacteriochlorophylls and derivatives causes dehydrogenation of pyrroline ring B preferentially over ring D. ,− Here, the trans -dialkyl-substituted ring D is susceptible to dehydrogenation, whereas the gem-dimethyl-substituted ring B is not. The reaction of bacteriochlorin BC-1 with DDQ at room temperature afforded the chlorin C-1 in 35% yield (Scheme , top).…”

“…Although BC-1 is composed of a mixture of diastereomers (epimers at the 13 2 -position), C-1 is expected as a pair of enantiomers. Relatively few ring-B chlorins containing an intact isocyclic ring are known (Scheme , bottom), all of which have been prepared by semisynthesis beginning with bacteriochlorophyll a (by selective dehydrogenation with FeCl 3 ) , or a porphyrin derived from chlorophyll a (by selective vicinal hydroxylation with OsO 4 ) . The known ring-B chlorins exhibit the following red-region absorption properties: C-2 , λ = 691 nm, ε 691nm = 4.31 × 10 4 M –1 cm –1 (CH 2 Cl 2 ); C-3 , λ = 682 nm, ε 682nm = 3.65 × 10 4 M –1 cm –1 (CH 2 Cl 2 /THF); and C-4 , λ = 683 nm (CH 2 Cl 2 ) …”

In Situ, Protein-Mediated Generation of a Photochemically Active Chlorophyll Analogue in a Mutant Bacterial Photosynthetic Reaction Center

“…Collectively, these findings led us to consider the possibility that Chl X is a variant of 3-AcChl a formed from BChl a by oxidation at the 17–18 position of ring D rather than at the normal 7–8 position of ring B (Figure and Figure S1-6). Seven examples of such transformations have been reported for demetalated forms of BChl/Chl analogues in solution. − In all but one case, the chlorin with ring D oxidized has a Q y band at a wavelength longer than that of the analogue that has ring B oxidized. (Here, oxidation refers to the 2e – , 2H + dehydrogenation at the β-positions of the pyrrolic ring.)…”

Autophagy Regulation and Photodynamic Therapy: Insights to Improve Outcomes of Cancer Treatment

“…Another parameter that drives PDT efficiency is the molecular structure of the PS. Of note, PSs belonging to the same class may have distinct properties, given the diversity of the side-groups that can be attached to the lead chromophore (25)(26)(27)(28)(29)(30)(31).…”